Thesis Defense: Frederick (Fritz) Seidl, Burns Group

Date
Mon March 5th 2018, 2:30 - 4:30pm
Location
Chemistry Gazebo

"Catalytic Enantioselective Dihalogenation of Allylic Alcohols"

Enantioselective dihalogenation is an important method for the total synthesis of stereocomplex polyhalogenated natural products, but only a few methods with significant limitations exist for this transformation. In 2015, we developed the chemo-, regio- and enantioselective bromochlorination of allylic alcohols featuring a titanium half-salen catalyst to help address this problem (Figure 0-1).[1],[2] The utility of this method has been demonstrated by the enantioselective total syntheses of 11 halogenated natural products to date by our lab, each of which was directly enabled by this method. Following development, we applied the enantioselective bromochlorination to various new substrates including homoallylic alcohols, which resulted in the total synthesis of (–)-anverene, a polyhalogenated marine natural product with modest but selective antibiotic activity.[3] Computational and experimental mechanistic work was undertaken to better understand the catalytic enantioselective bromochlorination, as well as the enantiospecific solvolysis of resulting enantioenriched bromochlorides.[4] The enantioselective dihalogenation catalyst system has also been extended to haloazidation using TMSN3 as the nucleophilic azide source.[5]



[1] Hu, D. X.*; Seidl, F. J.*; Bucher, C.; Burns, N. Z. “Catalytic Chemo-, Regio-, and Enantioselective Bromochlorination of Allylic Alcohols.” J. Am. Chem. Soc. 2015, 137, 3795–3798. *Equal contribution

[2] Seidl, F. J.; Burns, N. Z. “Catalytic Chemo-, Regio-, and Enantioselective Bromochlorination of Allylic Alcohols: (2S,3S)-3-bromo-2-chloro-3,7-dimethyl-6-octen-1-ol.” Org. Synth. Invited publication; manuscript in preparation.

[3] Seidl, F. J.; Burns, N. Z. “Selective bromochlorination of a homoallylic alcohol for the total synthesis of (–)-anverene.” Beilstein J. Org. Chem. 2016, 12, 1361–1365.

[4] Burckle, A. J.; Gal, B.; Seidl, F. J.; Vasilev, V. H.; Burns, N. Z. “Enantiospecific Solvolytic Functionalization of Bromochlorides.” J. Am. Chem. Soc. 2017, 139, 13562–13569.

[5] Seidl, F. J.*; Min, C.*; Lopez, J. A.; Burns, N. Z. “Catalytic Regio- and Enantioselective Haloazidation of Allylic Alcohols.” Manuscript in preparation. *Equal contribution